Novel neoadjuvant immunotherapy regimen safety and survival in head and neck squamous cell cancer

• Published in: Head & neck 2011-12, Vol.33 (12), p.1666-1674
• Main Authors: Wolf, Gregory T., Fee Jr, Willard E., Dolan, Robert W., Moyer, Jeffrey S., Kaplan, Michael J., Spring, Paul M., Suen, James, Kenady, Daniel E., Newman, Jason G., Carroll, William R., Gillespie, M. Boyd, Freeman, Scott M., Baltzer, Lorraine, Kirkley, Terry D., Brandwein, Harvey J., Hadden, John W.
• Format: Article
• Language: English
• Subjects: Acute toxicity; Adult; Aged; Antineoplastic Agents - administration & dosage; Biological and medical sciences; Cancer; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - therapy; Cell survival; Clinical trials; Cyclophosphamide - administration & dosage; cytokine; Cytokines; Cytokines - therapeutic use; Data collections; Disease-Free Survival; Drug Administration Schedule; Female; Gluconates - administration & dosage; Head; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - mortality; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - therapy; head and neck squamous cell carcinoma; Homeostasis; Humans; immune response; Immunity (cell-mediated); Immunotherapy; Indomethacin; Indomethacin - administration & dosage; Injections, Subcutaneous; Interferon-gamma - administration & dosage; Interleukin-1beta - administration & dosage; Interleukin-2 - administration & dosage; IRX-2; Male; Medical sciences; Middle Aged; Neck; Neoadjuvant Therapy; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; phase 2; Prognosis; Squamous cells; Survival; Survival Rate; Tumor Necrosis Factor-alpha - administration & dosage; Tumors; Zinc
• ISSN: 1043-3074; 1097-0347; 1097-0347
• DOI: 10.1002/hed.21660

Background Cellular immune suppression is observed in head and neck squamous cell cancer (HNSCC) and contributes to poor prognosis. Restoration of immune homeostasis may require primary cell‐derived cytokines at physiologic doses. An immunotherapy regimen containing a biologic, with multiple‐active cytokine components, and administered with cytoxan, zinc, and indomethacin was developed to modulate cellular immunity. Methods Study methods were designed to determine the safety and efficacy of a 21‐day neoadjuvant immunotherapy regimen in a phase 2 trial that enrolled 27 therapy‐naïve patients with stage II to IVa HNSCC. Methods included safety, clinical and radiologic tumor response, disease‐free survival (DFS), overall survival (OS), and tumor lymphocytic infiltrate (LI) data collection. Results Acute toxicity was minimal. Patients completed neoadjuvant treatment without surgical delay. By independent radiographic review, 83% had stable disease during treatment. OS was 92%, 73%, and 69% at 12, 24, and 36 months, respectively. Histologic analysis suggested correlation between survival and tumor LI. Conclusion Immunotherapy regimen was tolerated. Survival results are encouraging. © 2011 Wiley Periodicals, Inc. Head Neck, 2011